The K15 Protein of Kaposi's Sarcoma-Associated Herpesvirus Recruits the Endocytic Regulator Intersectin 2 through a Selective SH3 Domain Interaction

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• 作者：Caesar S. Lim ; Bruce T. Seet ; Robert J. Ingham ; Gerald Gish ; Liudmila Matskova ; Gö ; sta Winberg ; Ingemar Ernberg ; Tony Pawson
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：September 4, 2007
• 年：2007
• 卷：46
• 期：35
• 页码：9874 - 9885
• 全文大小：733K
• 年卷期：v.46,no.35(September 4, 2007)
• ISSN：1520-4995

文摘

Kaposi's sarcoma-associated herpesvirus, also known as human herpesvirus 8, is closelyassociated with several cancers including Kaposi's sarcoma, primary effusion lymphoma, and multicentricCastleman's disease. The rightmost end of the KSHV genome encodes a protein, K15, with multiplemembrane-spanning segments and an intracellular carboxy-terminal tail that contains several conservedmotifs with the potential to recruit interaction domains (i.e., SH2, SH3, TRAF) of host cell proteins. K15has been implicated in downregulating B cell receptor (BCR) signaling through its conserved motifs andmay thereby play a role in maintaining viral latency and/or preventing apoptosis of the infected B cells.However, K15's mode of action is largely unknown. We have used mass spectrometry, domain and peptidearrays, and surface plasmon resonance to identify binding partners for a conserved proline-rich sequence(PPLP) in the K15 cytoplasmic tail. We show that the PPLP motif selectively binds the SH3-C domainof an endocytic adaptor protein, Intersectin 2 (ITSN2). This interaction can be observed both in vitro andin cells, where K15 and ITSN2 colocalize to discrete compartments within the B cell. The ability of K15to associate with ITSN2 suggests a new role for the K15 viral protein in intracellular protein trafficking.